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妊娠糖尿病载脂蛋白C3基因Sst Ⅰ多态性与血脂关系的研究

Association Between Apolipoprotein C-3 Sst Ⅰ Polymorphism and Serum Lipids in Patients With Gestational Diabetes Mellitus

  • 摘要:
      目的  探讨妊娠糖尿病(GDM)患者血脂的改变是否与载脂蛋白C-3(APOC3)基因Sst Ⅰ酶切位点多态性有关。
      方法  应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测1027例正常妊娠对照者和630例GDM患者APOC3基因Sst Ⅰ多态性。酶法测定总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和血糖(Glu),化学发光法测定血浆胰岛素(INS)。免疫透射比浊法测定载脂蛋白A1(apoA1)和B(apoB)水平。
      结果  APOC3基因Sst Ⅰ多态位点S1和S2等位基因频率在GDM组和对照组分别为0.704/0.296和0.721/0.279。APOC3基因Sst Ⅰ多态性基因型频率、等位基因频率在GDM组和正常对照组间差异无统计学意义(P>0.05)。GDM组S2S2和S1S2基因型者与S1S1者相比,血浆HDL-C水平较高,而致动脉硬化指数(AI)值较低,差异有统计学意义(P均<0.05);GDM患者进一步划分为肥胖和非肥胖亚组后,APOC3基因型与HDL-C水平的关系仅在肥胖亚组观察到,而与AI值的关系在两个亚组均能观察到;此外,在肥胖GDM孕妇S2S2基因型者其血浆TG水平高于S1S1和S1S2型者(P<0.05,P<0.01),而非肥胖GDM孕妇S2S2型者其apoB/apoA1比值低于S1S1型携带者(P<0.05)。正常妊娠对照组未见上述血脂和载脂蛋白水平具有显著差异变化存在。
      结论  GDM患者APOC3基因Sst Ⅰ位点基因型与血浆HDL-C和TG含量以及AI和apoB/apoA1比值有一定的关系,其中血脂水平和载脂蛋白比值的变化具有体质量指数依赖的特征,但未见该位点与GDM的发生有关。

     

    Abstract:
      Objective  To investigate the apolipoprotein C-3 (APOC3) gene Sst Ⅰ polymorphism and its relationship with changes in serum lipids in patients with gestational diabetes mellitus (GDM).
      Methods  A total of 630 pregnant women with GDM and 1027 normal pregnant controls were covered in the study. The genotype and allele frequencies of APOC3 Sst Ⅰ polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence. Apolipoproteins A 1 (apoA1) and B (apoB) levels were measured by turbidimetric immunoassay.
      Results  The allele frequencies of S1 and S2 of the APOC3 polymorphism at the Sst Ⅰ locus were 0.704 and 0.296 in the GDM group and 0.721 and 0.279 in the control group, respectively. There was no significant difference in genotype frequency and allele frequency of APOC3 Sst Ⅰ polymorphism between the GDM and the control groups (P>0.05). In the GDM group, those with S2S2 and S1S2 genotypes had higher plasma HDL-C levels and lower atherogenic index (AI) values than those with S1S1 genotype did, with the differences being statistically significant (all P<0.05). GDM patients were then divided into obesity and non-obesity subgroups. Further subgroup analysis showed that the association of APOC3 genotype with changes in HDL-C levels was observed only in obese GDM patients, while the association of APOC3 genotype with changes in AI values was observed in both obese and nonobese patients. In addition, in obese GDM patients, those with S2S2 genotype had significantly higher plasma TG levels than those with S1S1 and S1S2 genotypes did (P<0.05 and P<0.01, respectively). In non-obese GDM patients, those with S2S2 genotype had significantly lower apoB/apoA1 ratio than S2S2 carriers did (P<0.05). No genotype-related effect on lipid and apolipoprotein variations was evident in the normal controls.
      Conclusion  APOC3 Sst Ⅰ polymorphism in GDM patients is associated with HDL-C and TG levels as well as AI value and apoB/apoA1 ratio. The changes in lipid levels and apolipoprotein ratio showed BMI-dependent features. However, association between polymorphism at the locus and the development of GDM was not observed.

     

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